Neurodegenerative disease research is one of UND's few recognized strengths as identified in 3 separate Strategic research reports. This COBRE Phase 111 funding request will support our neurodegenerative disease research group's administrative core, pilot grant program, and our mass spectrometry and imaging cores. Our COBRE group continues to focus on determining mechanisms responsible for the pathogenesis of and identifying possible therapeutic interventions against neurodegenerative disorders. Since our COBRE funding started 9 years ago, we supported 11 project directors, we developed and supported two cores, we supported the hiring of 9 neuroscience faculty, and we supported with pilot grants 16 neuroscience investigators. COBRE investigators received about $11M in extramural grants, published 242 manuscripts, and a new Neuroscience Research Building was built. Our Mass Spectrometry Core Facility is used almost exclusively for small molecule analysis including metabolomics, lipidomics, drug metabolism, molecule structure identification, and small molecule quantification. The equipment housed in our facility includes a new Waters Synapt G2 QTOF with UPLC and Nanomate, an API-3000 triple quadripole with HPLC, a QSTAR with nanoLC, a Polaris Q ion trap with GC, and a Beckman 2-D HPLC. Our Imaging Core Facility provides access to fluorescence, confocal, multiphoton, and electron microscopy instrumentation. The equipment housed in our facility includes two confocal microscopes (Zeiss 510 META LSCM, Olympus FV300 LSCM), a Zeiss ConfoCor2 fluorescence correlation spectroscopy unit, an Olympus FV1000MPE Basic multiphoton/visible confocal microscope system, and two fluorescence microscopes (Nikon TE300 equipped for FURA2 and CFP/YFP FRET ratiometric imaging, and a Nikon Eclipse 801). For electron microscopy, we have a scanning (Hitachi 4700) and a transmission (Hitachi 7500) electron microscope, Reichert ultra-microtomes, and a range of ancillary equipment. The COBRE grant-supported neurodegenerative disease research group has been supported strongly by UND, our successes are recognized by UND, and UND is fully committed to helping sustain our efforts after COBRE funding ends.